Comparison of proton therapy and photon therapy for early-stage non-small cell lung cancer: a meta-analysis.

The use of proton therapy (PT) in early-stage non-small cell lung cancer (ES-NSCLC) remains controversial, with insufficient evidence to determine its superiority over photon therapy (XRT). We conducted a systematic review of PT trials in ES-NSCLC, analyzing dosimetry, efficacy, and safety across to inform clinical decision-making. Our study showed that PT reduced lung and heart dosimetric parameters compared to XRT, with significant differences in lung V5, lung V10 and mean heart dose (MHD). In terms of efficacy, there were no significant differences in 1-year OS, 3-year OS and 3-year PFS between PT and XRT. For toxicity, no significant difference was observed in treatment-related adverse events (TRAEs) and radiation pneumonitis (RP). Single-arm analysis of PT found that V5, V10, V20 of lung and heart V5 were 13.4%, 11.3%, 7.9% and 0.7%, respectively. The mean lung dose and MHD were 4.15 Gy and 0.17 Gy, respectively. The single-arm pooled 1-, 2-, 3- and 5-year OS rates for PT were 95.3%, 82.5%, 81.3% and 69.3%, respectively. PFS rate and local control rate at 3 years were 68.1% and 91.2%, respectively. The rates of TRAEs of grade ≥ 3 and grade ≥ 2 were 2.8% and 19.8%, respectively. The grade ≥ 2 RP occurred at a rate of 8.7%. In conclusion, PT had acceptable efficacy and safety, and was better at protecting organs at risk than XRT in ES-NSCLC. However, the survival and safety benefit of PT was not significant compared to XRT.

A bibliometric analysis of light chain amyloidosis from 2005 to 2024: research trends and hot spots.

Background: Light chain (AL) amyloidosis stands as the most prevalent subtype of systemic amyloidosis, encompassing a group of rare diseases. Here, we evaluated the scientific landscape of AL amyloidosis to investigate research trends and identify hotspots within the field. Methods: Relevant studies on AL amyloidosis published over the past two decades were retrieved from the Web of Science Core Collection. The publications between 2005 and 2024 were subjected to bibliometric analyses, leveraging tools including CiteSpace, VOSviewer, RStudio and MS Excel to analyse and visualize the annual publication trend, co-occurrence patterns, collaborative networks among countries, organizations, and authors. Burst keywords and references were also examined to obtain the research history, and emerging hotspots. Results: The bibliometric analysis included 2,864 articles published between 2005 and 2024. The most productive journal is Amyloid-Journal of Protein Folding Disorders. The United States, along with several developed nations, emerges as a dominant force in international AL amyloidosis research. "AL amyloidosis" and "cardiac amyloidosis" were the primary hotspots over the past two decades, and "Biomarkers," "Cardiac amyloidosis," and "treatment" would be future trends. Conclusion: This bibliometric analysis examined the research developments in AL amyloidosis over the past two decades using bibliometric software. Recent research in this field primarily focuses on two main areas: clinical diagnosis and treatment of AL amyloidosis, as well as cardiac amyloidosis. Emphasis is placed on understanding the mechanisms underlying immunoglobulin light chain aggregation and deposition to mitigate organ involvement.

Utility of Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Diseases in Critically Ill Immunocompromised Pediatric Patients.

Purpose: Infections cause high rates of illness and death in children worldwide. However, studies on the clinical value of metagenomic next-generation sequencing (mNGS) for immunocompromised children are still limited. Patients and Methods: From June 2021 to December 2023, 119 samples were collected at Pediatric Intensive Care Unit (PICU) of a single-center pediatric hospital and classified into two groups based on their immune states. We compared the diagnostic performance of mNGS and conventional microbiological test (CMT) for pathogen identification, and assessed the clinical impacts of mNGS. Results: Among the 119 samples, 48 (40.34%) belonged to the immunocompromised children. mNGS had a higher positivity rate than CMT (76.47% vs 55.46%, P = 0.0006). The positive percent agreement (PPA) of mNGS for immunocompromised children was higher compared to immunocompetent children (95.24% vs 77.78%). The most common pathogens for immunocompromised patients were gram-negative bacteria and herpesvirus. However, immunocompetent children showed a higher detection rate for gram-positive bacteria and respiratory viruses. Furthermore, the proportions of the positive impact of mNGS results were significantly higher in immunocompromised patients compared to immunocompetent patients for both diagnosis (91.67% vs 57.75%) and treatment (95.83% vs 64.79%) (P < 0.0001). Immunocompromised state, length of hospital stays, times stay in ICU, Pediatric Risk of Mortality (PRISM) score, neutrophil percentage (NEUT%) and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) were considered independent factors for poor prognosis in critically ill pediatric patients. Conclusion: In patients from PICU, mNGS had a greater clinical significance in immunocompromised children compared to immunocompetent children. mNGS technology is an important auxiliary method for achieving accurate diagnosis and treatment of critically ill pediatric patients.

NXPH4 mediated by m5C contributes to the malignant characteristics of colorectal cancer via inhibiting HIF1A degradation.

OBJECTIVE: Colorectal cancer (CRC) is a form of malignancy that exhibits a comparatively elevated occurrence and fatality rate. Given the relatively slower progress in diagnostic and therapeutic approaches for CRC, there is a need to investigate more accurate and efficient biomarkers. METHODS: Core regulatory genes were screened using the TCGA database, and the expression of neurexophilin 4 (NXPH4) and its prognostic implications were validated using tissue microarray staining. The assessment of NXPH4 functions involved a range of experiments, including cellular, organoid, and murine models. Furthermore, a regulatory network between m5C, NXPH4, and HIF1A was established through several in vitro experiments. RESULTS: The overexpression of NXPH4 is associated with unfavorable prognoses in patients with CRC and hepatocellular carcinoma. Additionally, it facilitates the progression of malignant tumors both in laboratory settings and in living organisms of colorectal carcinoma. Our research also reveals that NXPH4 mRNA can avoid degradation through RNautophagy, relying on an m5C-dependent mechanism. Moreover, NXPH4 amplifies the HIF signaling pathway and stabilizes HIF1A by competitively binding to PHD4. CONCLUSIONS: NXPH4, regulated by m5C, promotes malignant tumor progression and regulates the HIF pathway. Consequently, targeting NXPH4 through molecular therapies could potentially serve as an efficacious therapeutic strategy for the management of CRC exhibiting elevated NXPH4 expression.

[Whole Process Analysis and Fate Behavior of Microplastics in Urban Wastewater Treatment Plants, Including their Occurrence Forms, Components, and Removal Efficiency].

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that： fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance； the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances （PET, PBT）, cellulose, and polypropylene （PP） were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was （73 ±5） n·L-1, the effluent abundance was （14 ±2） n·L-1, and the overall removal rate was （80.8 ±12.1）%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids （49.2 ±7.4）% and secondary sedimentation tanks （92.4 ±13.9）%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.

Molecularly imprinted photoelectrochemical sensor for ultrasensitive and selective detection of hydroquinone using 0D CdS nanoparticle/3D flower-like ZnIn2S4 microsphere nanocomposite.

A novel photoelectrochemical (PEC) sensor was developed for the ultra-sensitive and highly selective detection of hydroquinone (HQ), featuring a composite structure that combines 0D CdS nanoparticles with a 3D flower-like ZnIn2S4 microsphere. The sensor, termed rMIP/CdS/ZnIn2S4, employed molecularly imprinted polymers (MIPs) to achieve specific recognition of HQ. An p-phenylenediamine (pPD) polymer film was electrochemically polymerized onto the surface of the CdS/ZnIn2S4 composite-coated glassy carbon electrode (GCE). Through hydrogen bonding, HQ molecules were imprinted onto the polymer film. Subsequent elution removed these molecules, leaving behind specific recognition sites, enabling selective detection of HQ. The unique spatial structure and heterojunction properties of the 0D CdS nanoparticle/3D flower-like ZnIn2S4 composite, combined with molecular imprinting, significantly enhanced the photocurrent response and increased the selectivity and sensitivity for HQ detection. Under optimal conditions, the rMIP/CdS/ZnIn2S4 sensor demonstrated a low detection limit (0.7 nmol·L-1, S/N=3) over a wide linear range of 1-1200 nmol·L-1. The sensor was successfully applied to detect HQ in real water samples, showing promise for environmental pollution control applications.

An electrochemical ratiometric immunosensor for the detection of NMP22 based on ZIF-8@MWCNTs@Chit@Fc@AuNPs and AuPt-MB.

Nuclear matrix protein 22 (NMP22) is one of the most important tumor markers of bladder cancer and is significantly elevated in the urine of bladder cancer patients. Therefore, in this work, a highly sensitive ratiometric electrochemical immunosensor was constructed to detect NMP22 based on ZIF-8@MWCNTs@Chit@Fc@AuNPs composites. ZIF-8 had a large surface area and good adsorption ability. Multi-Walled Carbon Nanotubes (MWCNTs) can optimize the electrical conductivity of ZIF-8, so that the electrode surface of ferrocene (Fc) obtains a stable and strong electrochemical signal. In addition, AuPt-MB provided another strong detection signal methylene blue (MB) while immobilizing the secondary antibody (Ab2) through Au-N and Pt-N bonds. A ratiometric electrochemical sensor was formed based on ZIF-8@MWCNTs@Chit@Fc@AuNPs and AuPt-MB, which showed a great linear connection between IMB/IFc and the logarithmic concentration of NMP22 with a detection limit of 3.33 fg mL-1 (S/N = 3) under optimized specifications in the concentration interval of 0.01 pg mL-1 to 1000 ng mL-1. In addition, the ratiometric immunosensor showed good selectivity and stability.

Progression of m6A in the tumor microenvironment: hypoxia, immune and metabolic reprogramming.

Recently, N6-methyladenosine (m6A) has aroused widespread discussion in the scientific community as a mode of RNA modification. m6A comprises writers, erasers, and readers, which regulates RNA production, nuclear export, and translation and is very important for human health. A large number of studies have found that the regulation of m6A is closely related to the occurrence and invasion of tumors, while the homeostasis and function of the tumor microenvironment (TME) determine the occurrence and development of tumors to some extent. TME is composed of a variety of immune cells (T cells, B cells, etc.) and nonimmune cells (tumor-associated mesenchymal stem cells (TA-MSCs), cancer-associated fibroblasts (CAFs), etc.). Current studies suggest that m6A is involved in regulating the function of various cells in the TME, thereby affecting tumor progression. In this manuscript, we present the composition of m6A and TME, the relationship between m6A methylation and characteristic changes in TME, the role of m6A methylation in TME, and potential therapeutic strategies to provide new perspectives for better treatment of tumors in clinical work.

Sleep Deprivation Induces Gut Damage via Ferroptosis.

Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.

Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank.

BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%. CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.

Investigating the mechanism of Zn cross-linking of chitin in a mycelium-based leather substitute and its performance evaluation.

Mycelium-based leather substitutes with a three-dimensional reticulated structure have attracted attention owing to the negative environmental impacts of natural and synthetic leather. This study utilised Ganoderma lucidum mycelium to prepare a mycelium-based leather substitute with zinc cross-linking (MF-Zn) and evaluated its physicochemical properties and sensory performance; the conventional Cr3+ tanning method was used as reference. Results demonstrated that Zn2+ and Cr3+ formed cross-links with the -OH and -NHOCH3 groups in the polysaccharides of chitin, while Zn2+ selectively bonded to a fraction of -NH2 groups in cystine and phenylalanine. The mycelium-based leather substitute with Zn cross-linking exhibited impressive tensile strength and tear strength of 7.0 MPa and 16.4 kN/m, respectively, while demonstrating desirable organoleptic properties. The free radical-scavenging capacity of MF-Zn was assessed, revealing a DPPH radical and hydroxyl radical scavenging rates of 39.4% and 52.7%, respectively. By successfully investigating the cross-linking mechanism of mycelial fibres with Zn2+ and obtaining the stabilised mycelium-based leather substitute, this study establishes a fundamental basis for the development of sustainable leather substitutes, meeting the requirements and facilitating significant advancements in low-carbon leather substitute production.

Biochar alters the soil fauna functional traits and community diversity: A quantitative and cascading perspective.

With the widespread use of biochar, the cascading effects of biochar exposure on soil fauna urgently require deeper understanding. A meta-analysis quantified hierarchical changes in functional traits and community diversity of soil fauna under biochar exposure. Antioxidant enzymes (24.1 %) did not fully mitigate the impact of MDA (13.5 %), leading to excessive DNA damage in soil fauna (21.2 %). Concurrently, reproduction, growth, and survival rates decreased by 20.2 %, 8.5 %, and 21.2 %, respectively. Due to a 39.7 % increase in avoidance behavior of soil fauna towards biochar, species richness ultimately increased by 80.2 %. Compared to other feeding habits, biochar posed a greater threat to the survival of herbivores. Additionally, macrofauna were the most sensitive to biochar. The response of soil fauna also depended on the type, size, concentration, and duration of biochar exposure. It should be emphasized that as exposure concentration increased, the damage to soil fauna became more severe. Furthermore, the smaller the biochar sizes, the greater the damage to soil fauna. To mitigate the adverse effects on soil fauna, this study recommens applying biochar at appropriate times and selecting large sizes in low to medium concentrations. These findings confirm the threat of biochar to soil health from the perspective of soil fauna.

Impact of rehabilitation unit-based physical activity therapy versus symptomatic supportive treatment on older patients with advanced cancer: a non-randomized controlled study.

OBJECTIVES: Relatively few studies have investigated the effects of rehabilitation-based physical activity therapy as a treatment for older patients with advanced cancer. This study evaluated the effects of individualized precise and structured exercise interventions, prescribed by a rehabilitation physician, on fatigue, quality of life (QOL), and physical activity in older patients with advanced cancer. METHODS: After admission to the rehabilitation department, older cancer patients were divided into groups receiving conventional symptomatic supportive therapy (SST) or physical activity therapy plus conventional symptomatic supportive therapy (PAT). The SST group was given symptomatic supportive treatment, exercised on their own, and were observed at home after their symptoms improved. The PAT group was required to implement physical exercise along with SST, involving 30 min of moderate-intensity exercise per day and 5 days per week, and were discharged after 4 weeks and instructed to continue to exercise outside the hospital. Cancer-related fatigue (CRF) at 4 and 8 weeks was the primary endpoint of the study, while the secondary endpoints included patients' QOL, physical activity, and exercise adherence rate. RESULTS: Sixty-five patients were included; 37 (56.92%) chose to enter the PAT group, and 28 (43.08%) chose to enter the SST group. After 4 and 8 weeks of treatment, CRF relief and QOL improvement were significantly better in the PAT group than in the SST group (p < 0.05), whereas global health status did not differ between the two treatment groups (T1: p = 0.84; T2: p = 0.92). Mild physical activity significantly increased for the PAT group at T1 and T2 (T1: p = 0.03; T2: p = 0.005). At the T2 time point, the PAT group exhibited a higher level of participation in moderate-intensity physical activities as well as a higher total leisure activity score (p < 0.05). Thirty-three patients (94.29%) completed the PAT exercise program during hospitalization. Only four (12.12%) patients achieved moderate-intensity exercise, while the other 29 (87.88%) patients were able to continue exercising after their exercise intensity was decreased. CONCLUSIONS: Implementation of precise and individualized exercise interventions, prescribed by the rehabilitation team, can lead to the reduction of CRF and improvement of QOL, and change in behavior related to physical activity.

TNIP3 protects against pathological cardiac hypertrophy by stabilizing STAT1.

Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. Here, we identified the first evidence that TNFAIP3 interacting protein 3 (TNIP3) was a negative regulator of pathological cardiac hypertrophy. We observed a significant upregulation of TNIP3 in mouse hearts subjected to transverse aortic constriction (TAC) surgery and in primary neonatal rat cardiomyocytes stimulated by phenylephrine (PE). In Tnip3-deficient mice, cardiac hypertrophy was aggravated after TAC surgery. Conversely, cardiac-specific Tnip3 transgenic (TG) mice showed a notable reversal of the same phenotype. Accordingly, TNIP3 alleviated PE-induced cardiomyocyte enlargement in vitro. Mechanistically, RNA-sequencing and interactome analysis were combined to identify the signal transducer and activator of transcription 1 (STAT1) as a potential target to clarify the molecular mechanism of TNIP3 in pathological cardiac hypertrophy. Via immunoprecipitation and Glutathione S-transferase assay, we found that TNIP3 could interact with STAT1 directly and suppress its degradation by suppressing K48-type ubiquitination in response to hypertrophic stimulation. Remarkably, preservation effect of TNIP3 on cardiac hypertrophy was blocked by STAT1 inhibitor Fludaradbine or STAT1 knockdown. Our study found that TNIP3 serves as a novel suppressor of pathological cardiac hypertrophy by promoting STAT1 stability, which suggests that TNIP3 could be a promising therapeutic target of pathological cardiac hypertrophy and heart failure.

Emerging Roles and Therapeutic Applications of Arachidonic Acid Pathways in Cardiometabolic Diseases.

Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence has revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks and intimately participate in the progression and severity of cardiometabolic diseases. In this review, we systemically summarized and updated the biological functions of arachidonic acid pathways in cardiometabolic diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, and diabetes. We further discussed the cellular and molecular mechanisms of arachidonic acid pathway-mediated regulation of cardiometabolic diseases and highlighted the emerging clinical advances to improve these pathological conditions by targeting arachidonic acid metabolites and pathway factors.

Progress in Epigenetic Modification Regulating Drug Transporters in the Hypoxic Environment.

Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter levels in the hypoxic environment. In addition to being regulated by HIF-1, nuclear receptors, and inflammatory factors, hypoxia can also regulate transporters through epigenetic modifications, thereby affecting drug absorption, distribution, metabolism, and excretion. In recent years, increasing attention has been paid to the role of epigenetic modifications in regulating drug transporters under hypoxic conditions at high altitude. In this paper, we comprehensively review the effects of hypoxia on drug transporters and epigenetic modifications and explore the regulatory mechanism of epigenetic modifications on drug transporter expression under hypoxic conditions. The aim is to provide a reference for exploring the epigenetic regulation mechanism of drug transporter expression in the hypoxic environment at high altitude, and then guide the study of pharmacokinetics and promote effective and safe medication at high altitude.

Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis.

Objective: Gastric cancer (GC) is the world's third-leading cause of cancer-related mortality; the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers for early diagnosis and immune therapy response prediction. Here, we aim to discover the connection between chemokine ligand 14 (CCL14) expression in the gastric tumor microenvironment (TME) and its clinical significance and investigate its correlation with immune cell infiltration. Methods: We assessed CCL14 mRNA expression and its interrelation with tumor-infiltrating immune cells (TILs) using bioinformatics analysis in gastric cancer. CCL14 protein expression, TILs, and immune checkpoints were detected by multiple immunohistochemistry analyses in gastric cancer tissue microarrays. Then, we conducted statistics analysis to determine the association between CCL14-related patient survival and immune cell infiltration (p < 0.05). Results: We found that the CCL14 protein was separately expressed in the carcinoma cells and TILs in stomach cancer tissues. The CCL14 protein was related to tumor differentiation and tumor depth and positively correlated with the presentation of LAG3 and PD-L1 in gastric cancer cells. In addition, the CCL14 protein in the TILs of gastric cancer tissues was related to Lauren's type cells, T cells (CD4+ and CD8+), and CD68+ macrophages in the TME. Kaplan-Meier survival and multivariate analyses showed that the CCL14 expression in gastric cancer cells was an independent prognostic factor. Conclusion: Our study illustrated that CCL14 is a poor prognosis biomarker in gastric cancer, which may be associated with the potential for immunotherapy.

SCARB2 associates with tumor-infiltrating neutrophils and predicts poor prognosis in breast cancer.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in various aspects of breast cancer development and metastasis. Nevertheless, the expression, prognostic significance, and correlation with clinical features of SCARB2 in breast cancer, as well as the infiltrative characteristics of TME, remain largely unknown. METHODS: We analyzed the differential presentation of SCARB2 mRNA in breast cancer tissues and nontumorous breast tissues and prognosis by The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Additionally, the Tumor Immunity Estimation Resource (TIMER) was taken to evaluate the correlation between SCARB2 mRNA presence and tumor-infiltrating immune cells and immune checkpoints in the TME in breast cancer. We performed multiple immunohistochemical staining to verify the SCARB2 protein expression in breast cancer tissues and its relationship to immune cells and checkpoints and clinicopathological features. RESULTS: We identified elevated SCARB2 expression in breast cancer tissues, and high SCARB2 protein presentation was associated with advanced clinical stage and unfavorable prognosis. In addition, enhanced SCARB2 protein presence was closely correlated with up-regulation CD66b+ neutrophils infiltration in tumor tissues (r = 0.210, P < 0.05) and CD68 + CD163+ M2 macrophages in the interstitium (r = 0.233, P < 0.05), as well as the immune checkpoints, including PD-1 (r = 0.314, P < 0.01) protein expression. CONCLUSION: SCARB2 holds promise for predicting the clinical outcome of breast cancer patients and could serve as a potential therapeutic target.

BRG1 Deficiency Promotes Cardiomyocyte Inflammation and Apoptosis by Activating the cGAS-STING Signaling in Diabetic Cardiomyopathy.

Brahma-related gene 1 (BRG1) has been implicated in the repair of DNA double-strand breaks (DSBs). Downregulation of BRG1 impairs DSBs repair leading to accumulation of double-stranded DNA (dsDNA). Currently, the role of BRG1 in diabetic cardiomyopathy (DCM) has not been clarified. In this study, we aimed to explore the function and molecular by which BRG1 regulates DCM using mice and cell models. We found that BRG1 was downregulated in the cardiac tissues of DCM mice and in cardiomyocytes cultured with high glucose and palmitic acid (HG/PA), which was accompanied by accumulation of dsDNA and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. shRNA-mediated Brg1 knockdown aggravated DCM mice cardiac functions, enhanced dsDNA accumulation, cGAS-STING signaling activation, which induced inflammation and apoptosis. In addition, the results were further verified in HG/PA-treated primary neonatal rat cardiomyocytes (NRCMs). Overexpression of BRG1 in NRCMs yielded opposite results. Furthermore, a selective cGAS inhibitor RU.521 or STING inhibitor C-176 partially reversed the BRG1 knockdown-induced inflammation and apoptosis in vitro. In conclusion, our results demonstrate that BRG1 is downregulated during DCM in vivo and in vitro, resulting in cardiomyocyte inflammation and apoptosis due to dsDNA accumulation and cGAS-STING signaling activation. Therefore, targeting the BRG1-cGAS-STING pathway may represent a novel therapeutic strategy for improving cardiac function of patients with DCM.

Innovative Delivery System Combining CRISPR-Cas12f for Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Antimicrobial resistance poses a significant global challenge, demanding innovative approaches, such as the CRISPR-Cas-mediated resistance plasmid or gene-curing system, to effectively combat this urgent crisis. To enable successful curing of antimicrobial genes or plasmids through CRISPR-Cas technology, the development of an efficient broad-host-range delivery system is paramount. In this study, we have successfully designed and constructed a novel functional gene delivery plasmid, pQ-mini, utilizing the backbone of a broad-host-range Inc.Q plasmid. Moreover, we have integrated the CRISPR-Cas12f system into the pQ-mini plasmid to enable gene-curing in broad-host of bacteria. Our findings demonstrate that pQ-mini facilitates the highly efficient transfer of genetic elements to diverse bacteria, particularly in various species in the order of Enterobacterales, exhibiting a broader host range and superior conjugation efficiency compared to the commonly used pMB1-like plasmid. Notably, pQ-mini effectively delivers the CRISPR-Cas12f system to antimicrobial-resistant strains, resulting in remarkable curing efficiencies for plasmid-borne mcr-1 or blaKPC genes that are comparable to those achieved by the previously reported pCasCure system. In conclusion, our study successfully establishes and optimizes pQ-mini as a broad-host-range functional gene delivery vector. Furthermore, in combination with the CRISPR-Cas system, pQ-mini demonstrates its potential for broad-host delivery, highlighting its promising role as a novel antimicrobial tool against the growing threat of antimicrobial resistance.